Description (from applicant's abstract): The principal aim is to use rhesus macaques infected intravaginally with SIV as a model for HIV-1 transmission and a foundation of designing and evaluating vaccine candidates. Virus-cell relationships will be defined by in situ hybridization and PCR-based techniques and the cellular immune response will be identified and quantified. The proposal involves a consortium of investigators headed by Ashley Haase and includes Christopher Miller, David Watkins and Steven Wolinsky. In aim 1, two competing hypotheses will be tested following transmission: SIV replication is confined to the portal of entry for a sufficient time to allow an anamnestic immune defense to prevent dissemination vs. transmission leads to unimpeded spread in DCs and/or macrophages beyond the site of entry. In aim 2, they will examine the hypothesis that latently or chronically infected cells arise quickly after transmission. In aim 3, they will test the hypothesis that the balance between virus reproduction and the scope and breadth of the immune response determines the success or failure of establishing a persistent infection.